Fryns Microphthalmia Syndrome

Clinical Features

Although primary anophthalmia has been documented as a manifestation of several mental retardation/congenital anomaly (MCA) syndromes, as reviewed by Leichtman et al. (1994), the nosology of this group of disorders is confusing. Fryns et al. (1995) described an apparently distinct 'anophthalmia-plus' syndrome in sibs. The index patient was a female fetus at 17 weeks' gestation with bilateral anophthalmia, bilateral cleft lip/cleft palate, macrotia with bilateral lateral facial cleft, large open sacral neural tube defect, and uterus unicornis. The parents were normal and nonconsanguineous with an unremarkable family history. Their first child, a 4-year-old boy, was normal. The second child, a 2.5-year-old boy, had bilateral clinical anophthalmia and an abnormal left ear with absent lobule as the sole additional anomaly.

Warburg et al. (1997) described a patient with bilateral extreme microphthalmia and bilateral congenital glaucoma, bilateral medial oblique facial cleft ending in lid colobomas, bilateral stenosis of the choanae, bifid uvula, frontal encephalocele, and premature craniosynostosis. They suggested that this was an example of the Fryns anophthalmia syndrome, which may be an autosomal recessive disorder, although intrauterine environmental factors cannot be excluded.

Wiltshire et al. (2003) reported a boy with a nasal deformity, choanal atresia, bifid uvula, severe bilateral microphthalmia, and a facial cleft who showed regression of development at the age of 2 years with subsequent improvement.

Akalin et al. (2005) reported a male infant, born of consanguineous parents, with left-sided anophthalmia and right-sided microphthalmia with bilateral partial fusion of the eyelids, bilateral cleft lip and palate with nasal deformity, and clinodactyly of the right fourth toe. The patient was noted to have elevated serum levels of thyroid-stimulating hormone; thyroid ultrasonography revealed bilateral hyperplasia with no cysts or nodules. Akalin et al. (2005) concluded that primary hypothyroidism is an important additional feature of the 'anophthalmia-plus' syndrome.

Makhoul et al. (2007) described a male infant, born of nonconsanguineous parents, who had bilateral cleft palate and lip, mild microphthalmia with iris coloboma and glaucoma of the right eye, and blepharophimosis with severe microphthalmia of the left eye. Spine x-ray and MRI revealed first sacral hemivertebra with spina bifida, and agenesis of the second through fifth sacral vertebrae and coccyx, with caudal tethering of the spinal cord at L3, filum terminalis lipoma, and a syringomyelia. Brain ultrasound and MRI showed hypoplasia of corpus callosum with mild dilation of the lateral ventricles; orbital MRI showed a posteriorly located lens of the left eye and a split vitreous body in the right eye, suggestive of primary hyperplastic vitreous. In contrast to the patient reported by Akalin et al. (2005), this patient had normal serum levels of free thyroxine, TSH, and cortisol. Makhoul et al. (2007) stated that this case supported the notion of anophthalmia-plus as a distinct syndrome.

Ozalp et al. (2008) reported a 26-week female fetus with bilateral clinical anophthalmia, agenesis of the upper lip and palate, cerebral ventricular dilation, adrenal hypoplasia, and single umbilical artery. A neural tube defect was not detected. Histologic examination of adrenal tissue showed a focal pseudofollicular pattern, autolytic changes, and neuroblastic clusters in the adrenal cortex. The consanguineous Turkish parents had a healthy 7-year-old daughter from their first pregnancy; a male infant from their second pregnancy had frontal bossing, bilateral anophthalmia, total agenesis of the upper lip, and rudimentary nostrils, and died at 9 weeks of age due to respiratory and cardiac failure. Ozalp et al. (2008) stated that this was the first report of adrenal hypoplasia in Fryns anophthalmia-plus syndrome.

Inheritance

Fryns et al. (1995) suggested autosomal recessive inheritance of the disorder.

Nomenclature

See 309800 for discussion of misuse of the term 'anophthalmia' in the medical literature.